Erythromycins A through D, represented by formula (E),
______________________________________ ##STR1## Erythromycin R.sup.a R.sup.b ______________________________________ A OH CH.sub.3 B H CH.sub.3 C OH H D H H ______________________________________
are well-known and potent antibacterial agents, used widely to treat and prevent bacterial infection.
Some erythromycin derivatives having the formula I below possess an expected degree of prokinetic activity and are described in U.S. Pat. No. 5,578,579. ##STR2##
The preparation of these prokinetic compounds requires the preparation of the intermediate compounds, N-desmethyl-4"-deoxy-erythromycin A and N-desmethyl-4"-deoxy-erythromycin B.
One procedure for the preparation of N-desmethyl derivatives of various macrolide antibiotics has been described in U.S. Pat. No. 3,725,385, issued Apr. 3, 1973, which teaches that the methyl group may be removed by a one-step treatment with a single addition of iodine in a pH-adjusted solution from -10.degree. C. to 50.degree. C. The N-desmethylation step with iodine does not generally go to completion, leaving a substantial amount of the starting material with the final product.
There is, therefore, a need to provide an improved and more efficient process for the manufacture of the 3'-N-substituted derivatives of 8,9-anhydro-erythromycin-6,9-hemiketals.